MDACC 2018: The Evolving Role of Epigenetics in Renal Cell Carcinoma

Houston, Texas (UroToday.com) Dr. Ho, speaking as the 2018 David A. Swanson Distinguished Alumni lecturer for the Department of GU Medical Oncology, noted that kidney cancer can be thought of as an epigenetic disease. SETD2, a gene that encodes a non-redundant methyltransferase responsible for histone H3 lysine 36 trimethylation (H3K36me3), undergoes loss-of-function mutations in clear cell renal cell carcinomas.

Dr. Ho’s group demonstrated that the loss of H3K36 methylation is associated with higher cancer-specific mortality compared with H3K36me3-positive tumors1. Dr. Ho and his team demonstrated that in renal epithelial cell lines that have been artificially induced to undergo epithelial to mesenchymal transition (EMT), when compared with SETD2-deficient cells, epithelial markers are lost in the absence of SETD2. This suggests that SETD2 plays a key role in the EMT process. Further, renal metastases were found to be enriched with a clonal population with decreased H3K36me3, and loss of H3K36me3 is additionally associated with EMT.

MDACC 2018 Dr. Thai Ho

Dr. Ho also presented data that demonstrated that extracellular matrix disulfide bridges can be therapeutically targeted with small molecules or monoclonal antibodies, and altering the tumor-stroma ECM can change the penetration of cytotoxic agents, antibodies, and immune cells into tumor cell population.


Presented by: Thai Ho, MD, Ph.D., Assistant Professor, Division of Hematology/Oncology, Mayo Clinic, Phoenix, Arizona

References:
1. Ho TH, Kapur P, Joseph RW, Serie DJ, Eckel-Passow JE, Tong P, et al. Loss of histone H3 lysine 36 trimethylation is associated with an increased risk of renal cell carcinoma-specific death. Mod Pathol [Internet]. 2016 Jan;29(1):34–42.

Written by: Dr. Vikram M. Narayan (@VikramNarayan), Urologic Oncology Fellow with Ashish M. Kamat, MD (@UroDocAsh), Professor, Department of Urology, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX at the 13th Update on the Management of Genitourinary Malignancies, The University of Texas (MDACC - MD Anderson Cancer Center) November 9-10, 2018, Dan L. Duncan Building, Houston, TX